George W. Hay

The rapid synthesis of deoxyfluoro sugars using tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF)

Deoxyfluoro sugars were synthesized rapidly by the reaction of trifluoromethanesulfonyl derivatives of partially protected sugars with tris(dimethylamino)sulfonium difluorotrimethylsilicate (TASF) under mild conditions. The displacements occurred with inversion of configuration; fluorine has been introduced stereospecifically at each of the secondary alcoholic sites of aldohexopyranosides and in one example of a furanoid system. In some instances unsaturated compounds that contained no fluorine were produced.

Spectrophotometric methods to determine carbohydrates in soil

Abstract Two common spectrophotometric procedures for determining neutral carbohydrates—the phenol-sulfuric acid and anthrone methods were evaluated for soil analysis. The phenol-sulfuric acid procedure gives results comparable to those obtained by gas-liquid chromatography, and is applicable to a variety of soil types. Prior removal of interfering substances by anion and cation exchange is required. Glucose is recommended as the spectrophotometric reference standard. The anthrone method is not satisfactory under the conditions employed.

Synthesis and characterization of 1-O-β-lactosyl-(R,S)-glycerols and 1,3-di-O-β-lactosylglycerol☆

Abstract The synthesis of 1- O -β-lactosyl-( R,S )-glycerols was achieved by three methods: ( a ) in 25% yield by the trimethylsilyl trifluoromethanesulfonate-promoted reaction of octa- O -acetyl-β-lactose ( 11 ) with ∼0.5 mol-equiv. of 2- O -benzylglycerol ( 4 ), ( b ) in ∼34% yield by the coupling of 4 with an equimolar amount of hepta- O -acetyl-α-lactosyl bromide ( 12 ) in the presence of mercury(II) cyanide, and ( c ) in ∼50% yield by the coupling of equimolar amounts of 12 and 1,2-di- O -benzyl-( R,S )-glycerols in the presence of mercury(II) cyanide, followed in each case by the removal of the blocking groups. 1,3-Di- O -β-lactosylglycerols were prepared in 21% yield by the coupling of 11 with ∼0.5 mol-equivalent of 4 by method ( a ), and in 38% yield by the coupling of 12 with ∼0.5 mol-equiv. of 4 by method ( b ), followed by the removal of the blocking groups. The configuration of the glycosidic linkage between the lactose units and the glycerol residue was established by high-resolution, two-dimensional 1 H-n.m.r. spectroscopy.

Studies on the synthesis of novel carbohydrates with sulphur in the ring. Part II. Analogues of derivatives of unsaturated deoxy-ulopyranosidonic acids via Diels–Alder reactions with methyl cyanodithioformate

3,6-Dihydro-2-methylthio-2H-thiopyran-2-carbonitrile (5) and its 3-methoxy-derivative (11) were obtained directly from the Diels–Alder reactions of methyl cyanodithioformate (4) with buta-1,3-diene and trans-1-methoxy-buta-1,3-diene, respectively. The regioselectivity of the reagent (4) is opposite to that of carbonyl dienophiles with 1-alkoxybuta-1,3-dienes. The structure of compound (11) was established by 1H n.m.r. studies involving compounds (5) and (11) and their selectively oxidized and/or reduced derivatives. The results indicated that (11) exists predominantly in the 0H2 conformation in chloroform.

Synthesis and characterization of 2-O-β-lactosylglycerol, 1,2-di-O-β-lactosyl-(R,S)-glycerols, and 1,2,3-tri-O-β-lactosylglycerol

Abstract The reaction of 2,3,6,2′,3′,4′,6′-hepta- O -acetyl-α-lactosyl bromide ( 5 ) and 1,3-di- O -benzylglycerol in the presence of mercury(II) cyanide in benzene-nitromethane afforded 1,3-di- O -benzyl-2- O -(2,3,6,2′,3′,4′, 6′-hepta- O -acetyl-β-lactosyl)glycerol (70%), which was converted into 2- O -β-lactosylglycerol. 1,2-Di- O -β-lactosyl-( R,S )- glycerols were obtained by way of the coupling of 5 to either 1- O -benzyl-( R,S )-glycerol or 1- O -benzyl-2- O -(2,3,6,2′,3′,4′,6′-hepta- O -acetyl-β-lactosyl)-( R,S )-glycerols. The most efficient route to 1,2, 3-tri- O -β-lactosylglycerol ( 17 ) involved treatment of 2- O -(2,3,6,2′,3′,4′,6′-hepta- O -acetyl-β-lactosyl)glycerol with 3 mol. equiv. of 5 followed by removal of the blocking groups, to give 17 (47%).

Synthesis and characterization of 1-O-α-lactosyl-(R,S)-glycerols and 1-O-α-lactosyl-3-O-β-lactosyl-(R,S)-glycerols

Abstract Coupling of 2,3,6,2′,3′,4′,6′-hepta- O -benzyl-α-lactosyl bromide with an equimolar amount of 1- O -acetyl-2- O -benzyl-( R,S )-glycerols in the presence of tetraethylammonium bromide and 4A molecular sieves in 1,2-dichloroethane afforded 3- O -acetyl-2- O -benzyl-1- O -(2,3,6,2′,3′,4′,6′-hepta- O -benzyl-α-lactosyl)-( R,S )-glycerols in 20.4% yield, which were deprotected to give 1- O -α-lactosyl-( R,S )-glycerols. 2- O -Benzyl-3- O -(2,3,6,2′,3′,4′,6′-hepta- O -acetyl-β-lactosyl)-1- O -(2,3,6,2′,3′,4′,6′-hepta- O -benzyl-α-lactosyl) -( R,S )-glycerols were obtained in 61% yield by the reaction of hepta- O -acetyl-α-lactosyl bromide and 2- O -benzyl-1- O -(2,3,6,2′,3′,4′,6′-hepta- O -benzyl-α- lactosyl)-( R,S )-glycerols in the presence of mercury(II) cyanide in benzene-nitromethane; deprotection afforded 1- O -α-lactosyl-3- O -β-lactosyl-( R,S )-glycerols in an overall yield of 24%. The two target materials are useful in the assessment of the binding properties of d -galactosyl-terminated glyceryl glycosides to the asialoglycoprotein receptor of normal rabbit and human hepatocytes.

Binding of D-galactose-terminated ligands to rabbit asialoglycoprotein receptor.

The binding affinities of a series of D-galactose-terminated glycerol glycosides and oligosaccharides for the asialoglycoprotein receptor isolated from rabbit liver were determined in vitro using a radioreceptor-inhibition assay with 125I-asialoorosomucoid. The relative affinities of the synthetic ligands increased with the number of exposed D-galactose termini. Of the compounds examined, 1,2,3-tri-O-beta-lactosylglycerol associated with the greatest affinity (estimated Kd = 7.97 x 10(-5) M). Examination of the affinities of the synthetic series indicated that both the number and propinquity of the D-galactose termini influenced the strength of the binding interactions.

The carbohydrates of the leaves of common barberry (berberis vulgaris). The extraction, fractionation and structural studies of selected non-cellulosic polysaccharides☆

Abstract Common barberry leaves contain a small but diverse polysaccharide fraction which afforded an α-glucan, a β-xylan, and three neutral, and two galacturonic acid-containing glucoxylans. Only the α-glucan was devoid of protein. The α-glucan is primarily (1→4)-linked, but some residues are branched through C-3 or C-6. Two of the neutral glucoxylans contained small proportions of both D -galactose and L -arabinopyranose in terminal, non-reducing locations, the third neutral glucoxylan contained no arabinose; all were branched through both glucose and xylose residues. Hydrolysis of one of these heteropolysaccharides with pectinase afforded a new disaccharide, 4-O-α- D -xylopyranosyl- D -glucopyranose, thus establishing that at least some of the linkages were of the α-type. A new approach to the structural determination of micro quantities of oligosaccharides is discussed.

Reaction of 1,2-anhydro-3,4:5,6-di-O-isopropylidene-1-C-nitro-d-mannitol with potassium hydrogenfluoride in ethylene glycol: a synthesis of 2-deoxy-2-fluoro-d-glucose☆

The reaction of 1,2-anhydro-3,4:5,6-di-O-isopropylidene-1-C-nitro-d-mannitol (2) with potassium hydrogenfluoride in ethylene glycol under anhydrous conditions provides a route to 2-deoxy-2-fluoro-d-glucose, the 18F-labeled analog of which is an important radiopharmaceutical of use in medical imaging. The reaction is accompanied to a minor extent by epimerization at C-2 of the initially formed fluoro aldehyde and also results in an attack by solvent at C-2 in 2.

A synthesis of 2-deoxy-d-arabino-hexitol and its oxidation to 5-deoxy-d-hreo-hexulose (“5-deoxy-d-fructose”) using immobilized cells of Gluconobacter oxydans

Abstract 2-Deoxy- d - arabino -hexitol ( 6 ) was obtained by borohydride reduction of 2-deoxy- d - arabino -hexose ( 5 ). The synthesis of 5 , starting from 2,3:4,5-di- O -isopropylidene- d -arabinitol ( 1 ), was achieved by a one-carbon chain-elongation involving formylation of the Grignard reagent derived from 1-bromo-1-deoxy-2,3:4,5-di- O -isopropylidene- d -arabinitol ( 2 ), using lithium formate, followed by hydrolytic removal of the isopropylidene groups. Immobilized cells of Gluconobacter oxydans (ATCC 15178) selectively oxidized 6 to give 5-deoxy- d - threo -hexulose ( 7 ) in 65% yield (∼9% overall yield from 1 ).